Progression of peripheral occlusive arterial disease in diabetes mellitus. What factors are predictive?

The clinical, biochemical, and vascular laboratory measurements potentially associated with the development and/or progression of peripheral occlusive arterial disease (POAD) were assessed during a 4-year period in 110 normal control subjects, 112 patients with POAD without diabetes mellitus, 240 patients with diabetes mellitus without POAD, and 100 patients with diabetes mellitus and POAD. Age, history of hypertension or coronary heart disease, history of cigarette smoking, presence of POAD, systolic blood pressure, and beta-thromboglobulin level were associated with progression of POAD. A multivariate logistic regression model indicated that the presence of diabetes mellitus or POAD or both at baseline, decreased postexercise ankle-brachial index, increased arm systolic blood pressure, and current smoking were independently associated with progression of POAD. This study suggests that cessation of smoking and control of hypertension are essential treatment modifications to decrease the risk of progression of peripheral vascular disease in diabetic patients.

Course of peripheral occlusive arterial disease in diabetes. Vascular laboratory assessment.

To determine comparative rates of development and progression of peripheral occlusive arterial disease, 110 healthy nondiabetic control subjects, 112 patients with peripheral occlusive arterial disease (POAD), 240 patients with diabetes mellitus (DM), and 100 patients with diabetes mellitus and peripheral occlusive arterial disease (DM + POAD) were studied over 4 yr with noninvasive techniques. The presence of peripheral occlusive arterial disease was determined by postexercise ankle-brachial index (ABI) values; progression of peripheral occlusive arterial disease was determined by the rate of change in postexercise ABI. Patients who underwent peripheral arterial reconstructive surgery or amputation were also classified as having progression of their peripheral occlusive arterial disease. On this basis, follow-up revealed that peripheral occlusive arterial disease developed and therefore progressed in 1 (1%) of the control group and 22 (9%) of the DM. Peripheral occlusive arterial disease progressed in 31 (28%) of the POAD and 26 (26%) of the DM + POAD. The presence of peripheral occlusive arterial disease predisposes to progression of disease, and peripheral occlusive arterial disease is more likely to develop in diabetic patients who do not have peripheral occlusive arterial disease than in nondiabetic control subjects. However, the presence of diabetes mellitus in patients with peripheral occlusive arterial disease does not seem to increase the risk of progression.

Sterol excretion and cholesterol absorption in diabetics and nondiabetics with and without hyperlipidemia.

Fecal neutral and acidic sterols and cholesterol absorption were measured in 12 normal control subjects, 40 diabetic subjects with and without hyperlipidemia, and 27 subjects with hyperlipidemia but without diabetes mellitus. All subjects were on a low-cholesterol diet (less than 300 mg cholesterol/day). Fecal excretion of neutral and acidic sterols was increased in patients with hypertriglyceridemia and was more marked in diabetic patients with hypertriglyceridemia. Cholesterol absorption was decreased in diabetic patients with hypertriglyceridemia. Otherwise, there were no significant differences in sterol excretion or cholesterol absorption in diabetic and nondiabetic subjects compared with control groups with similar lipid levels. The best predictors of fecal neutral- and acidic-sterol excretion and of estimated cholesterol synthesis were very low [corrected]-density lipoprotein triglycerides and high-density lipoprotein cholesterol. Correction of hyperlipidemia may be beneficial in decreasing cholesterol synthesis and, thereby, in decreasing the risk of atherogenesis.

Extramural cross-validation of the Mayo primary biliary cirrhosis survival model establishes its generalizability.

The generalizability of the Mayo model for predicting survival in individual primary biliary cirrhosis patients without liver transplantation was tested and confirmed. The model was applied to a data base of patients from the New England Medical Center Hospitals (n = 141) and the Scott and White Clinic (n = 35) and found to predict their survival accurately. It was also shown to be accurate for Mayo primary biliary cirrhosis patients with very advanced disease (n = 30), those with less than a 33% chance of surviving 12 months. The analyses confirmed that the addition of histologic stage did not significantly improve the predictive power of the model (p greater than 0.10). We suggest that the Mayo model is a practical tool for clinical management and decision making.

Primary biliary cirrhosis: prediction of short-term survival based on repeated patient visits.

The progression of primary biliary cirrhosis was studied in 312 patients who were seen at the Mayo Clinic between January 1974 and May 1984. Follow-up was extended to April 30, 1988, by which time 140 of the patients had died and 29 had undergone orthotopic liver transplantation. These patients generated 1,945 patient visits that enabled us to study the change in the prognostic variables of primary biliary cirrhosis (age, bilirubin value, albumin value, prothrombin time and edema) from the time of referral. Also, using this database and the Cox proportional-hazards regression model, we developed an updated model for primary biliary cirrhosis that can be used to predict short-term survival at any time in the course of the disease. This model uses the values of the prognostic variables measured at the latest patient visit. Comparison of predicted survival from the update model and the natural history model of primary biliary cirrhosis showed that the updated model was superior to the original model for predicting short-term survival. This finding applied to both the Mayo Clinic patients and an independent set of 83 Dutch patients. The Mayo updated model is recommended for improving the accuracy of predictions of survival during the 2 yr after a patient visit.

Efficacy of hepatic transplantation in patients with primary sclerosing cholangitis.

Controlled trials to assess the therapeutic benefit of orthotopic hepatic transplantation (OHTx) for primary sclerosing cholangitis (PSC) cannot be justified in view of improvement of patient survival after this operation since 1981. However, the actual patient survival with OHTx can be compared with the Mayo model estimated survival probabilities without OHTx. This model, which encompasses physical, biochemical and histopathologic parameters of PSC, was constructed from a study of 392 conservatively treated PSC patients at five international centers in England and North America. We compared the actual survival of 216 adult patients with the diagnosis of advanced PSC who underwent hepatic replacement with the expected survival estimated by the Mayo PSC natural history model, "the simulated control technique." OHTx was performed at the University of Pittsburgh and Mayo Medical Center between 5 December 1981 and 26 December 1990. The mean (plus or minus standard deviation) post-OHTx follow-up period was 34 +/- 25 months (range of zero to 104 months). Before transplantation, biliary or portal hypertensive operation, or both, was performed upon 104 patients. At operation, the mean age of recipients was 42.1 +/- 11.3 years and the mean value of total serum bilirubin was 13.3 +/- 13.0 milligrams per deciliter. Extensive septal fibrosis and cirrhosis were histologically documented in 97 percent of the patients, with splenomegaly in 63 percent. Immunosuppressive therapy was based primarily on cyclosporin in 184 recipients and FK-506 in 32. Within six months, the Kaplan-Meier survival probability after OHTx (0.89) already was higher than predicted by the Mayo model (0.83). At five years, the Kaplan-Meier actual survival with OHTx was 0.73 compared with 0.28 expected Mayo model survival. The overall increased survival rate with transplantation was statistically significant (chi-square equals 126.6; p < 0.001). At all risk stratifications, OHTx significantly improved survival with a p value of 0.031 (low risk), 0.001 (moderate risk) and < 0.001 (high risk). Thus, OHTx is effective therapy for PSC. Disease gravity and unsuspected cholangiocarcinoma in the excised native liver adversely influenced short and long term survival rates after transplantation, respectively.